�Researchers at the NYU Cancer Institute and the Ronald O. Perelman Department of Dermatology have identified mebendazole, a drug secondhand globally to treat parasitical infections, as a novel investigational agent for the treatment of chemotherapy-resistant malignant melanoma.
Because most patients with metastatic melanoma fail to react to useable therapies, the discovery of a viable investigational discourse with an established safe profile could address a serious unmet need in oncology. Effectively sidestepping the prohibitive costs and long lead multiplication typically required to discover new genus Cancer medicines, the NYU squad screened a library of already approved drugs for activity against the near deadly shape of skin cancer.
Their report, which was selected for throw out online publication by Molecular Cancer Research, is promulgated in the August consequence of the journal. Since submitting the article for publication, the authors have conducted extra pre-clinical studies of mebendazole in an in vivo model of chemotherapy-resistant malignant melanoma and ar now preparing a phase angle I clinical trial, expected to start next year at NYU Cancer Institute.
"While rational drug plan remains a perfectly valid way to develop crab therapies, we also penury approaches that are less costly and more productive of new effective treatments," said lead author Seth J. Orlow, M.D. Ph.D., Chair of the Ronald O. Perelman Department of Dermatology at New York University School of Medicine. "You could say this is more than of a guerrilla approach. Instead of screening millions of untested compounds for an factor that inhibits or stimulates a special molecular target, we chose to screen a turgid library of already approved drugs for novel activity against malignant melanoma cells, and then upgrade the to the highest degree promising candidate rapidly to clinical practice."
First, the NYU researchers screened a library of 2,000 well-known drugs [Spectrum Collection (Microsource Discovery Systems)] and identified members of the benzimidazole kinsperson for their ability to inhibit melanoma growth and induce programmed cell death (apoptosis) of malignant malignant melanoma cells without affecting normal melanocytes (pigment-producing cells). Of the identified benzimidazoles, the team selected mebendazole for further work because it was known to be a well-tolerated, orally available drug with anti-cancer properties.
In a surprising find, the team found that mebendazole takes advantage of a exceptional difference 'tween a malignant melanoma cell and normal melanocytes. Melanomas produce high levels of a protein called Bcl-2, which is known to protect certain cancer cells from apoptosis. The team sawing machine that when a malignant melanoma cancer cell was exposed to mebendazole, it resulted in inactivation of Bcl-2, allowing programmed cell death to occur.
Mebendazole, sold as a generic drug in the United States, has been used since the 1970s to process roundworm, hookworm, pinworm, whipworm, and other worm-based parasitical infections. Previous research has shown it to have some anticancer activity in lung and adrenocortical crab.
"Our ability to identify novel treatments for melanoma and advance them chop-chop into the clinic identical much depends on NYU's multidisciplinary approaching to melanoma care and research," Dr. Orlow aforesaid. "To be effective, translational medicine cannot be unidirectional. Discovery moves continuously back and forward between the clinic and the bench. We are now focused on determining the chain of mountains of doses to be tested in the clinic, whether specific types of melanomas will respond better than others, and whether combining mebendazole with other agents testament be of further benefit"
The authors of this study are NYU Cancer Institute researchers Nicole Doudican, Adrianna Rodriguez, Iman Osman, and Seth J. Orlow. The study was supported by private beneficent grants.
NYU Langone Medical Center / New York University School of Medicine
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